Infection with herpes simplex type 1 (HSV-1) induces expression of receptors for C3b on mammalian cells previously devoid of such receptors. We have shown that the isolated glycoprotein responsible for this activity (gC) is a potent modulator of complement-mediated cytolysis in-vitro, acting by at least two mechanisms. Recently, we have demonstrated that herpes simplex type 2 (HSV-2) also induces expression of a C3b binding protein which corresponds to HSV-1 gC, but has different regulatory properties vis-a-vis the complement cascade. We have demonstrated that HSV-1 gC cannot support degradation of C3b, but does enhance the activity of the normal plasma C3b regulatory proteins. HSV-1 gC does not appear to fundamentally alter the interaction of human cellular C3b receptors (CR1) or iC3b receptors (CR3) with fluid phase or target-bound C3b or iC3b. Investigations in this area are ongoing. Studies have been initiated to examine the interactions of complement and antibody in neutralization of para-influenza virus. We have found that para-influenza virus 3 activates complement via the classical pathway in the absence of antibody. This activation is innocuous to the virus unless antibody is present, in which case neutralization and frank viral disruption occur. The antibody effect appears independent of the overall rate or extent of C3 deposition, and can be readily shown with monoclonal antibodies lacking intrinsic neutralizing capacity. Further studies will be directed at elucidating the mechanism of this IgG-complement interplay in viral neutralization.